Acta Pharmaceutica Sinica B,
Journal Year:
2024,
Volume and Issue:
14(7), P. 3027 - 3048
Published: March 12, 2024
Endothelial-to-mesenchymal
transition
(EndMT)
is
a
key
driver
of
atherosclerosis.
Aerobic
glycolysis
increased
in
the
endothelium
atheroprone
areas,
accompanied
by
elevated
lactate
levels.
Histone
lactylation,
mediated
lactate,
can
regulate
gene
expression
and
participate
disease
regulation.
However,
whether
histone
lactylation
involved
atherosclerosis
remains
unknown.
Here,
we
report
that
lipid
peroxidation
could
lead
to
EndMT-induced
increasing
lactate-dependent
H3
lysine
18
(H3K18la)
vitro
vivo,
as
well
atherosclerotic
patients'
arteries.
Mechanistically,
chaperone
ASF1A
was
first
identified
cofactor
P300,
which
precisely
regulated
enrichment
H3K18la
at
promoter
SNAI1,
thereby
activating
SNAI1
transcription
promoting
EndMT.
We
found
deletion
inhibited
EndMT
improved
endothelial
dysfunction.
Functional
analysis
based
on
ApoeKOAsf1aECKO
mice
model
confirmed
involvement
endothelium-specific
deficiency
alleviated
development.
Inhibition
pharmacologic
inhibition
advanced
PROTAC
attenuated
H3K18la,
transcription,
This
study
illustrates
precise
crosstalk
between
metabolism
epigenetics
via
P300/ASF1A
molecular
complex
during
atherogenesis,
provides
emerging
therapies
for
Advanced Materials,
Journal Year:
2024,
Volume and Issue:
36(26)
Published: April 7, 2024
Abstract
Brain
disorders
represent
a
significant
challenge
in
medical
science
due
to
the
formidable
blood–brain
barrier
(BBB),
which
severely
limits
penetration
of
conventional
therapeutics,
hindering
effective
treatment
strategies.
This
review
delves
into
innovative
realm
biomimetic
nanodelivery
systems,
including
stem
cell‐derived
nanoghosts,
tumor
cell
membrane‐coated
nanoparticles,
and
erythrocyte
membrane‐based
carriers,
highlighting
their
potential
circumvent
BBB's
restrictions.
By
mimicking
native
properties,
these
nanocarriers
emerge
as
promising
solution
for
enhancing
drug
delivery
brain,
offering
strategic
advantage
overcoming
barrier's
selective
permeability.
The
unique
benefits
leveraging
membranes
from
various
sources
is
evaluated
advanced
technologies
fabricating
membrane‐encapsulated
nanoparticles
capable
masquerading
endogenous
cells
are
examined.
enables
targeted
broad
spectrum
therapeutic
agents,
ranging
small
molecule
drugs
proteins,
thereby
providing
an
approach
neurocare.
Further,
contrasts
capabilities
limitations
with
traditional
methods,
underlining
enable
targeted,
sustained,
minimally
invasive
modalities.
concluded
perspective
on
clinical
translation
underscoring
transformative
impact
landscape
intractable
brain
diseases.
Cardiovascular Research,
Journal Year:
2024,
Volume and Issue:
120(3), P. 223 - 236
Published: Feb. 1, 2024
Abstract
Endothelial
cells
(ECs)
line
the
luminal
surface
of
blood
vessels
and
play
a
major
role
in
vascular
(patho)-physiology
by
acting
as
barrier,
sensing
circulating
factors
intrinsic/extrinsic
signals.
ECs
have
capacity
to
undergo
endothelial-to-mesenchymal
transition
(EndMT),
complex
differentiation
process
with
key
roles
both
during
embryonic
development
adulthood.
EndMT
can
contribute
EC
activation
dysfunctional
alterations
associated
maladaptive
tissue
responses
human
disease.
During
EndMT,
progressively
changes
leading
expression
mesenchymal
markers
while
repressing
lineage-specific
traits.
This
phenotypic
functional
switch
is
considered
largely
exist
continuum,
being
characterized
gradation
transitioning
stages.
In
this
report,
we
discuss
plasticity
potential
reversibility
hypothesis
that
different
EndMT-derived
cell
populations
may
disease
progression
or
resolution.
addition,
review
advancements
field,
current
technical
challenges,
well
therapeutic
options
opportunities
context
cardiovascular
biology.
Acta Pharmaceutica Sinica B,
Journal Year:
2024,
Volume and Issue:
14(7), P. 3027 - 3048
Published: March 12, 2024
Endothelial-to-mesenchymal
transition
(EndMT)
is
a
key
driver
of
atherosclerosis.
Aerobic
glycolysis
increased
in
the
endothelium
atheroprone
areas,
accompanied
by
elevated
lactate
levels.
Histone
lactylation,
mediated
lactate,
can
regulate
gene
expression
and
participate
disease
regulation.
However,
whether
histone
lactylation
involved
atherosclerosis
remains
unknown.
Here,
we
report
that
lipid
peroxidation
could
lead
to
EndMT-induced
increasing
lactate-dependent
H3
lysine
18
(H3K18la)
vitro
vivo,
as
well
atherosclerotic
patients'
arteries.
Mechanistically,
chaperone
ASF1A
was
first
identified
cofactor
P300,
which
precisely
regulated
enrichment
H3K18la
at
promoter
SNAI1,
thereby
activating
SNAI1
transcription
promoting
EndMT.
We
found
deletion
inhibited
EndMT
improved
endothelial
dysfunction.
Functional
analysis
based
on
ApoeKOAsf1aECKO
mice
model
confirmed
involvement
endothelium-specific
deficiency
alleviated
development.
Inhibition
pharmacologic
inhibition
advanced
PROTAC
attenuated
H3K18la,
transcription,
This
study
illustrates
precise
crosstalk
between
metabolism
epigenetics
via
P300/ASF1A
molecular
complex
during
atherogenesis,
provides
emerging
therapies
for
